Date of Award

1-1-2017

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (ii, xi, 88 pages) : illustrations (some color)

Dissertation/Thesis Chair

Douglas S Conklin

Committee Members

Bruce J Herron, Jason I Herschkowitz, Paul J Higgins, JoEllen Welsh

Keywords

Adipocytes, Breast Cancer, CD36, HER2, Lipotoxicity, NR1D1, Breast, HER-2 protein, HER-2 gene, Lipids, Hormone receptors, Adipose tissues

Subject Categories

Genetics | Molecular Biology

Abstract

Overexpression of HER2 (ERBB2/neu) in breast cancer is an established clinical marker for aggressive disease and increased mortality. HER2+ breast cancers have increased protein levels of Human Epidermal Growth Factor Receptor 2 and overexpression of its coding gene, ERBB2. Many HER2+ tumors feature concomitant co-expression of the Nuclear Receptor subfamily 1, Group D, Member 1 (NR1D1/RevERBα) which regulates adipogenesis and circadian rhythm; the dysregulation of these two processes are known risk factors for breast cancer. HER2+ breast cancer cells have increased lipid synthesis, with evidence suggesting that NR1D1 is responsible for the upregulation of several genes in the de novo lipid synthesis pathway. This enhanced lipogenic phenotype may support glucose metabolism and energy storage, exacerbating cancer progression.

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